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Astrocyte-Specific IL-1RI Signaling Effects Following Traumatic Brain Injury

Award Number: K08NS110829
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/15/2019
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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Astrocyte-Specific IL-1RI Signaling Effects Following Traumatic Brain Injury - Abstract The goals of the proposed mentored award are two-fold: 1) to provide protected time for intensive mentored research to develop Dr. Newell into an independent physician-scientist with a focus on the immune response to traumatic brain injury (TBI) and 2) to identify cell-type specific mechanisms that drive IL-1RI induced inflammation and neurotoxicity following TBI. In the United States, 1.7 million adults & 600,000 children suffer from TBI each year. Unfortunately, pharmacologic therapies for TBI are non-existant. Treatment strategies that target specific secondary injury cascades that follow TBI are critically needed. Inflammation driven by IL-1 and other pro-inflammatory cytokines is one potential secondary injury pathway. Using a fluid percussion injury model of TBI in mice, a mixed focal and diffuse injury is created with an accompanying inflammatory reaction similar to what occurs in human TBI. We have recently shown genetic blockade of IL-1RI signaling resulted in decreased neuroinflammation and improved cognitive function post-TBI. The hypothesis of this proposal is that astrocyte-specific IL-1RI signaling results in direct neurotoxicity as well as in microglial and leukocyte activation. The proposed studies will identify astrocyte-specific contributions of IL-1 induced secondary injury post-TBI. In the first aim, we will examine the impact of IL-1RI signlaling on astrocyte phenotype and the impact of IL-1 activated astrocytes on neurodegeneration. In the second aim, we will examine the impact of astrocyte IL-1RI signaling on microglial activation and brain leukocyte recruitment following TBI. At the same time, the proposed project is designed to provide critical career development training to the candidate. The proposal builds upon the candidate's established interest in TBI and her prior training in TBI modeling and neuroimmunology. The candidate will be mentored by senior faculty members with extensive experience in neuroscience, neuroimmunology, and pre-clinical TBI research. Through the expertise of her mentoring committee, exceptional scientific environment, formal coursework, and acquired scientific skills, Dr. Newell will be well positioned as a developing independent physician-scientist by the conclusion of the mentoring period.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$3,800 )
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/20/2024	NON-COMPETING CONTINUATION	-$3,800
														Subtotal = -$3,800

Issue Date FY: 2023 ( Subtotal = $188,128 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/24/2023	NON-COMPETING CONTINUATION	$188,128
														Subtotal = $188,128

Issue Date FY: 2022 ( Subtotal = $188,128 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/15/2022	NON-COMPETING CONTINUATION	$188,128
														Subtotal = $188,128

Issue Date FY: 2021 ( Subtotal = $187,128 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/3/2021	NON-COMPETING CONTINUATION	$187,128
														Subtotal = $187,128

Issue Date FY: 2020 ( Subtotal = $187,128 )
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/24/2020	NON-COMPETING CONTINUATION	$187,128
														Subtotal = $187,128

Issue Date FY: 2019 ( Subtotal = $187,128 )
2019	2019	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/11/2019	NEW	$187,488
2019	2019	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	3/19/2019	NEW	-$360
														Subtotal = $187,128

Grand Total All Awards = $933,840

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Astrocyte-Specific IL-1RI Signaling Effects Following Traumatic Brain Injury

Award Number: K08NS110829

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/15/2019

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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